ATE199090T1 - Gegenüber eigenen inhibitoren resistente t-pa mutanten - Google Patents

Gegenüber eigenen inhibitoren resistente t-pa mutanten

Info

Publication number
ATE199090T1
ATE199090T1 AT90905081T AT90905081T ATE199090T1 AT E199090 T1 ATE199090 T1 AT E199090T1 AT 90905081 T AT90905081 T AT 90905081T AT 90905081 T AT90905081 T AT 90905081T AT E199090 T1 ATE199090 T1 AT E199090T1
Authority
AT
Austria
Prior art keywords
mutants
serine protease
inhibitors
mutants resistant
encode
Prior art date
Application number
AT90905081T
Other languages
English (en)
Inventor
Joseph F Sambrook
Edwin L Madison
Elizabeth J Goldsmith
Maryjane H Gething
Robert D Gerard
Original Assignee
Univ Texas
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US07/434,748 external-priority patent/US5550042A/en
Application filed by Univ Texas filed Critical Univ Texas
Application granted granted Critical
Publication of ATE199090T1 publication Critical patent/ATE199090T1/de

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6456—Plasminogen activators
    • C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C07K14/8132—Plasminogen activator inhibitors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70—Vectors or expression systems specially adapted for E. coli
    • C12N15/71—Expression systems using regulatory sequences derived from the trp-operon
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6427—Chymotrypsins (3.4.21.1; 3.4.21.2); Trypsin (3.4.21.4)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21069—Protein C activated (3.4.21.69)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/10—Plasmid DNA
    • C12N2800/108—Plasmid DNA episomal vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/55—Vector systems having a special element relevant for transcription from bacteria
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
AT90905081T 1989-03-06 1990-03-01 Gegenüber eigenen inhibitoren resistente t-pa mutanten ATE199090T1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US31921289A 1989-03-06 1989-03-06
US07/434,748 US5550042A (en) 1989-03-06 1989-11-13 Serine protease mutants of the chymotrypsin superfamily resistant to inhibition by their cognate inhibitors and genes encoding the same and serine protease inhibitor mutants and genes encoding the same
PCT/US1990/000947 WO1990010649A1 (en) 1989-03-06 1990-03-01 Serpin resistant chymotrypsin superfamily proteases, particularly pai-1 resistant +-pa, complementary inhibitor mutants; compositions; genes; expression

Publications (1)

Publication Number Publication Date
ATE199090T1 true ATE199090T1 (de) 2001-02-15

Family

ID=23241316

Family Applications (2)

Application Number Title Priority Date Filing Date
AT90905081T ATE199090T1 (de) 1989-03-06 1990-03-01 Gegenüber eigenen inhibitoren resistente t-pa mutanten
AT00109138T ATE226636T1 (de) 1989-03-06 1990-03-01 Serpin-resistenter t-pa; mutanten; gene

Family Applications After (1)

Application Number Title Priority Date Filing Date
AT00109138T ATE226636T1 (de) 1989-03-06 1990-03-01 Serpin-resistenter t-pa; mutanten; gene

Country Status (10)

Country Link
US (1) US5728564A (de)
EP (2) EP0462207B1 (de)
JP (3) JP2991769B2 (de)
AT (2) ATE199090T1 (de)
AU (1) AU637791B2 (de)
CA (1) CA2047702C (de)
DE (2) DE69033699T2 (de)
DK (2) DK1029921T3 (de)
ES (2) ES2185529T3 (de)
WO (1) WO1990010649A1 (de)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5714145A (en) * 1988-09-02 1998-02-03 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties
US5262170A (en) * 1988-09-02 1993-11-16 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties and substituted at amino acid positions 296-299, DNA molecules encoding them, vectors, and host cells
US5866413A (en) * 1989-03-06 1999-02-02 Board Of Regents Of The University Of Texas System Pai-1 mutants
CA2071630C (en) * 1989-12-29 2000-02-22 Donald C. Foster Hybrid protein c
US5358932A (en) * 1989-12-29 1994-10-25 Zymogenetics, Inc. Hybrid protein C
GB9011861D0 (en) * 1990-05-26 1990-07-18 Beecham Group Plc Novel compounds
ES2067326T3 (es) * 1990-12-18 1995-03-16 Genentech Inc Variante especifica de activador de plasminogeno tisular.
ATE246000T1 (de) * 1992-06-03 2003-08-15 Genentech Inc Varianten des gewebeplasminogenaktivators mit verbesserter therapeutischer wirkung
GB9216558D0 (en) * 1992-08-04 1992-09-16 British Bio Technology Modified proteases
US5567602A (en) * 1992-08-12 1996-10-22 Arris Pharmaceutical Corporation Recombinant production of chymase
ES2080657B1 (es) * 1993-09-27 1996-11-01 Britisch Bio Technology Limite Proteasas modificadas.
EP0958833A1 (de) * 1998-05-20 1999-11-24 Erasmus Universiteit Rotterdam Verfahren und Mittel zur Vorbeugung oder Behandlung der Entzündung
AUPP508798A0 (en) 1998-08-05 1998-08-27 Biotech Australia Pty Limited Method of treating psoriasis
WO2001066771A2 (en) * 2000-03-03 2001-09-13 Zymogenetics, Inc. Human serine protease
US6673623B1 (en) 2000-09-12 2004-01-06 Novocure, Inc. Methods and compositions that control lipid production
WO2002072786A2 (en) 2001-03-13 2002-09-19 Corvas International, Inc. Nucleic acid molecules encoding a transmembrane serine protease 7, the encoded polypeptides and methods based thereon
WO2002077263A2 (en) 2001-03-22 2002-10-03 Dendreon San Diego Llc Nucleic acid molecules encoding serine protease cvsp14, the encoded polypeptides and methods based thereon
EP1379637A4 (de) 2001-03-27 2005-04-06 Dendreon Corp Transmembran-serinprotease 9 codierende nukleinsäuremoleküle, die codierten polypeptide sowie darauf beruhende verfahren
WO2002092841A2 (en) 2001-05-14 2002-11-21 Dendreon San Diego Llc Nucleic acid molecules encoding a transmembrane serine protease 10, the encoded polypeptides and methods based thereon
US7001872B2 (en) * 2001-06-11 2006-02-21 Halliburton Energy Services, Inc. Subterranean formation treating fluid and methods of fracturing subterranean formations
US20050137094A1 (en) * 2001-06-11 2005-06-23 Halliburton Energy Sevices, Inc. Subterranean formation treatment fluids and methods of using such fluids
US6488091B1 (en) * 2001-06-11 2002-12-03 Halliburton Energy Services, Inc. Subterranean formation treating fluid concentrates, treating fluids and methods
AU2002315525A1 (en) * 2001-07-03 2003-01-21 Dendreon San Diego Llc Nucleic acid molecules encoding a transmembrane serine protease 20, the encoded polypeptides and methods based thereon
WO2003053921A2 (en) * 2001-07-18 2003-07-03 American Red Cross Mutant proteinase inhibitors and uses thereof
US20030134794A1 (en) * 2001-11-20 2003-07-17 Madison Edwin L. Nucleic acid molecules encoding serine protease 17, the encoded polypeptides and methods based thereon
US20040001801A1 (en) * 2002-05-23 2004-01-01 Corvas International, Inc. Conjugates activated by cell surface proteases and therapeutic uses thereof
BRPI0409557B8 (pt) * 2003-04-04 2021-05-25 Univ Lausanne proteína recombinante inibidora de calicreína, sequência de dna, vetor de expressão, composição farmacêutica, uso da composição farmacêutica, método de produção da proteína recombinanete e kits de diagnóstico
ES2372709T3 (es) 2006-07-05 2012-01-25 Catalyst Biosciences, Inc. Procedimientos de cribado de proteasas y proteasas identificadas por los mismos.
JP2022516725A (ja) 2018-12-28 2022-03-02 カタリスト・バイオサイエンシーズ・インコーポレイテッド 改変ウロキナーゼ型プラスミノゲンアクティベータポリペプチドおよび使用方法
US11613744B2 (en) 2018-12-28 2023-03-28 Vertex Pharmaceuticals Incorporated Modified urokinase-type plasminogen activator polypeptides and methods of use
CN112375131B (zh) * 2020-11-16 2021-10-01 西南大学 Seroin蛋白的截短体及其应用

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5112755A (en) * 1982-04-15 1992-05-12 Genentech, Inc. Preparation of functional human urokinase proteins
AR241654A1 (es) * 1982-05-05 1992-10-30 Genentech Inc Procedimiento para producir activador de plasminogeno de tejido humano.
AU560584B2 (en) * 1983-07-28 1987-04-09 Bayer Aktiengesellschaft Homologues of aprotinin
US5073494A (en) * 1985-04-22 1991-12-17 Genentech, Inc. Human tissue plasminogen activator substituted at position 275 or at positions 275 and 277
JPH084501B2 (ja) * 1987-03-20 1996-01-24 エーザイ株式会社 糖鎖に関する変異ｔＰＡ
MY103358A (en) * 1987-04-15 1993-06-30 Novartis Ag Process for the production of protiens.
NO882226L (no) * 1987-05-22 1988-11-23 Zymogenetics Inc Fibrinolytiske proteiner.
US5200340A (en) * 1987-05-22 1993-04-06 Zymogenetics, Inc. Thrombin-activated tissue plasminogen activators
GB2208511A (en) * 1987-08-07 1989-04-05 Bayer Ag Variants of bovine pancreatic trypsin inhibitor produced by recombinant dna technology
US5188829A (en) * 1987-08-19 1993-02-23 Sagami Chemical Research Center Rapidly acting prourokinase
JPH04500752A (ja) * 1988-02-05 1992-02-13 ジェンザイム・コーポレーション 修飾ｔＰＡをコードする修飾遺伝子配列、並びにその産物
JPH03505276A (ja) * 1988-02-05 1991-11-21 ジェンザイム・コーポレーション 再配列された組織プラスミノーゲン活性化因子及びその産生方法
US5108901A (en) * 1988-09-02 1992-04-28 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties
US5262170A (en) * 1988-09-02 1993-11-16 Genentech, Inc. Tissue plasminogen activator having zymogenic or fibrin specific properties and substituted at amino acid positions 296-299, DNA molecules encoding them, vectors, and host cells

Also Published As

Publication number Publication date
AU637791B2 (en) 1993-06-10
CA2047702A1 (en) 1990-09-07
EP1029921B1 (de) 2002-10-23
JP3076035B2 (ja) 2000-08-14
DE69033699D1 (de) 2001-03-15
DK1029921T3 (da) 2003-02-24
DE69034013T2 (de) 2003-07-31
EP0462207A1 (de) 1991-12-27
EP0462207A4 (en) 1992-06-24
US5728564A (en) 1998-03-17
JP2991769B2 (ja) 1999-12-20
DE69033699T2 (de) 2001-05-23
CA2047702C (en) 2000-10-24
AU5278090A (en) 1990-10-09
ES2154629T3 (es) 2001-04-16
WO1990010649A1 (en) 1990-09-20
JP3076034B2 (ja) 2000-08-14
ATE226636T1 (de) 2002-11-15
EP1029921A1 (de) 2000-08-23
EP0462207B1 (de) 2001-02-07
DK0462207T3 (da) 2001-06-18
JP2000037195A (ja) 2000-02-08
JP2000078990A (ja) 2000-03-21
DE69034013D1 (de) 2002-11-28
JPH04504952A (ja) 1992-09-03
ES2185529T3 (es) 2003-05-01

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Legal Events

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EELA Cancelled due to lapse of time